This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There has been controversy related to the management of non-muscle invasive bladder cancer, which invades the lamina propria (pT1). This stage of bladder cancer has a significant propensity for recurrence and progression. We need to further understand the role of immunotherapy and/or whether this form of therapy should be optimized in order to improve therapeutic intervention of early stage bladder cancer, especially in those patients with recurrence of their tumor in the context of adjuvant BCG therapy. On the basis of the ability of interferon-inducible CXC chemokines to promote Th1 immunity and inhibit angiogenesis, we have coined the term, "immunoangiostasis" for their potential biological role in promoting tumor regression. Recently, we have identified the importance of the biology of immunoangiostasis in mediating tumor regression related to renal cell carcinoma. In this proposal, we hypothesize that the biology of immunoangiostasis is critical to the full success of adjuvant immunotherapy with BCG in patients with non-muscle invasive bladder cancer. Moreover, we postulated that in patients who fail to respond to this type of adjuvant therapy,, failure is due to their inability to manifest a full immunoangiostatic effect to their tumor. This latter concept would also suggest that there may be immunoangiostatic mechanisms that could be further optimized in order to fully mediate immunoangiostasis in these tumors. The protocol submitted for review will be used to determine whether the expression of interferon-inducible CXC chemokines in patients with non-muscle invasive bladder can be used as a biomarker to predict those patients that will respond vs. patients that will fail to respond to immunotherapy.